POS0319 THE COURSE OF SYMPTOMS IN CLINICALLY SUSPECT ARTHRALGIA AND ITS RELATION WITH SUBCLINICAL JOINT-INFLAMMATION DURING PROGRESSION TO RA: IS IT SIMILAR IN ACPA-POSITIVE AND ACPA-NEGATIVE DISEASE?
Authors: S. Khidir, D. Krijbolder, H. K. Glas, E. Van Mulligen, A. Van der Helm – van Mil
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> ACPA-positive and ACPA-negative RA have differences in genetic and environmental risk factors and in the severity of the disease course after diagnosis. However, the clinical presentation at RA-diagnosis is similar, as is the clinical presentation in the at-risk stage of clinically suspect arthralgia (CSA). We hypothesized that these clinical similarities at the end of the trajectory of RA-development imply a shared path in symptom development and progression before diagnosis. So far the course of symptoms during progression from CSA to RA and the association with the course of subclinical joint-inflammation is unknown. <h3>Objectives</h3> We studied the course of cardinal symptoms and subclinical joint-inflammation and the longitudinal relation in ACPA-positive and ACPA-negative disease. Relations were also studied in CSA-patients who did not develop RA. <h3>Methods</h3> CSA-patients from the Leiden CSA-cohort (n=664) and the placebo-arm of the TREAT EARLIER trial (n=117) were followed on development of inflammatory arthritis (IA) at physical examination, during which 136 patients developed IA and 645 did not. Symptoms of morning stiffness, pain and fatigue (with a numerical rating scale: 0-100) and presenteeism (productivity loss at work with the WPAI-questionnaire: 0-100%) were assessed at baseline and 4/12/24 months thereafter. Subclinical joint-inflammation (sum of synovitis/tenosynovitis/osteitis) was assessed at baseline and upon IA-development with contrast-enhanced 1.5T MRI of hand/foot. Linear and Poisson mixed models were used. <h3>Results</h3> Of the patients with IA-development, 66 (49%) were ACPA-positive. Both in ACPA-positive and ACPA-negative patients, symptoms (morning stiffness, presenteeism, fatigue) and subclinical joint-inflammation increased towards IA-development, and decreased or stabilized in patients without IA-development (Figure 1A). The course of pain, morning stiffness and presenteeism were significantly associated with the course of subclinical joint-inflammation in ACPA-positive CSA-patients during progression to RA. In ACPA-negative CSA-patients developing ACPA-negative RA, these effect sizes were smaller and not statistically significant (Figure 1B). Although the group-size of ACPA-positive CSA-patients not developing RA was smaller (n=47) than that of ACPA-negative non-progressing CSA (n=555), also here the decrease in symptoms seemed to have a stronger relationship with decreasing joint-inflammation in ACPA-positive than in ACPA-negative patients. <h3>Conclusion</h3> The severity of symptom development before diagnosis in ACPA-positive RA relates more strongly to increasing subclinical joint-inflammation than in ACPA-negative RA. This points towards differences in processes underlying the disease burden in ACPA-positive and ACPA-negative RA. Legend: A) Lines depict the course of symptoms (left y-axis) and subclinical joint-inflammation (right y-axis). This is shown separately for CSA-patients who did not develop RA; Figure A left, and those who did develop RA; Figure A right. B) Demonstrated are the effect sizes of 1 point increase in subclinical joint-inflammation over time on increase in symptoms over time. E.g. a beta of 0.8 for pain in ACPA-positive patients developing RA, implies that 1 point increase in inflammation over time gives 0.8 point more pain during the course towards RA-development. Abbreviations: ACPA= anti-citrullinated protein antibodies; CSA= clinically suspect arthralgia; RA=rheumatoid arthritis. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.